Sacubitril, the chemical name is 4-(((2S,4R)-1-([1,1′-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoic acid, the structure is as following:

U.S. FDA approved the anti-heart failure (anti-HF) drug Entresto (known as LCZ696) on July, 2015, which is a complex of the angiotensin II inhibitor valsartan and the enkephalinase inhibitor sacubitril. Valsartan can improve vasodilation and stimulate the body to excrete sodium and water, and sacubitril can block the mechanism of action of two peptides that threaten to lower blood pressure, thus LCZ696 is known as a dual inhibitor of angiotensin II receptor and enkephalinase, its clinical manifestation is a unique mode of action, which is superior to the standard drugs with respect to antihypertensive effect and the efficacy of reducing heart failure.
Some methods of preparing sacubitril are disclosed in the prior art, such as:
Patent application WO2008031567A1 disclosed a method of preparing biphenyl butyric acid substituted on 4 position amino or derivative thereof by using biphenyl propanol substituted on 2 position amino as starting materials, which was oxidized to aldehyde, and the aldehyde was suffered from Witting reaction to give biphenyl butenoic acid substituted on 4 position amino or derivative thereof, and the biphenyl butenoic acid substituted on 4 position amino or derivative thereof was suffered from a reduction reaction under H2 in the presence of transition metal of group 7, 8 and 9 in the chemical periodic table as catalyst and a chiral ligand, and then chiral separation to give biphenyl butyric acid substituted on 4 position amino or derivative thereof. The product can be converted to sacubitril. The process of the method is depicted as follows:

Patent application WO2008083967A2 disclosed a method of preparing sacubitril using 2-carbonylproline as a starting material, which was suffered from carboxy activation, biphenyl substitution, carbonyl reduction, chiral methylation, ring opening reaction and amide condensation and so on to give sacubitril. The reaction is depicted as follows:

The synthetic routes disclosed in patent applications WO 2008031567A1 and WO 2008083967A2 have some differences in the use of the raw materials, forming method of chirality and order of unit reactions, however, there are disadvantages such as difficulty in obtaining chiral raw materials, many reaction steps, expensive chiral catalytic reduction catalysts, poor stereoselectivity, and repeated use of carboxy or amino protection and deprotection, it is difficult to achieve industrialization smoothly.
Chiral induction agent (S)-1-(α-aminobenzyl)-2-naphthol (S-betti Base) with 2R-methyl-4-oxo-butanoic acid were suffered from cyclization, addition, debenzylation, ring opening, esterification and amidation and so on to give sacubitril disclosed in CN104557600A. The process is depicted as follows:

The process of preparing sacubitril has disadvantages of expensive and not readily available S-betti Base and chiral starting materials, preparation of Grignard reagent before addition reaction, strict reaction conditions, uncontrollable, and more cumbersome synthetic route.